Sleep Respiratory Disorders are disorders in which the flow rate into the lungs decreases during sleep to levels that are less than what is required to maintain normal blood gas tensions (PCO2 and PO2). Respiratory efforts increase in response, resulting in arousal from sleep or snoring depending on the severity and mechanism of the disorder and response characteristics of the respiratory control mechanisms. Sleep respiratory disorders manifest in different forms; Sleep Apnea, Snoring, and Respiratory Effort-Related Arousals (RERAs). Often the different forms are present in the same patient. The current invention should be beneficial in all these forms.
DIAGNOSIS OF SLEEP-RELATED RESPIRATORY DISORDERS: This is typically done overnight in a sleep laboratory or in the home by attaching a number of sensors to the body. A type of sensor that is essential for diagnosing such respiratory disorders is one that can sense the rate of air moving in and out of the patient. It is the pattern of change in such a signal that makes it possible to identify the presence of different types of disturbances. At present, there are three types of sensors that are used for this purpose. Because none of these is free of serious technical problems, it is customary to use all three in the same study. These sensors are: a) Nasal cannula pressure. Here, an open-ended tube is inserted in the nares. Changes in pressure at the tip of the tube are used to derive a semi-quantitative measure of flow. Although, when conditions are favorable, the signal provides a reasonably good indication of “relative” flow, conditions are frequently unfavorable such as when the nares is blocked or when the patient is breathing through the mouth. Also, the signal often becomes zero (i.e. signaling no flow), when some flow is still present, making it difficult to distinguish between apneas and hypopneas. b) Thermister: Here, a temperature sensitive sensor is placed in front of the nose and/or mouth. Changes in temperature are used to infer the direction and magnitude of flow. This signal cannot be quantified and is prone to serious drifts and artifacts, limiting its use to simply distinguish between, flow and no flow. c) Chest and abdomen bands: These are typically applied to the rib cage and abdomen. Changes in the impedance or inductance of these bands are used to infer changes in lung volume. Because changes in rib cage and abdomen dimensions are often not in phase with each other, it is necessary to perform complex calibrations to obtain the net change in lung volume. These calibrations also change frequently from time to time, making it impractical to use these signals for quantitative evaluation of breathing. As a result, the use of these bands is currently limited to determining if there are respiratory efforts and whether the rib cage and abdomen move in phase.
The current invention represents a totally new approach to monitoring breathing. Here, the subject wears an inflatable vest, cuff or garment with a pliable inner lining and a stiff outer lining. The vest is slightly pressurized (only 2-3 cmH2O) on a continuous basis to cause the inner lining to mould around the subject's torso without causing any significant reduction in lung volume. Under these conditions expansion of the lungs will result in air moving out of the vest, and vice versa. The flow in and out of the vest (Vest Flow) can be measured. This signal reflects air moving in and out of the lungs regardless of whether such air movement results in expansion of the rib cage, the abdomen or both, whether the rib cage and abdomen move in-phase or out-of-phase and whether the patient is breathing through the nose or mouth. With some minor adjustments to the Vest Flow signal, the signal can even be made purely quantitative, a feature that is now only achievable by attaching accurate flow meters to face masks.
TREATMENT OF SLEEP-RELATED RESPIRATORY DISORDERS: Sleep apnea is a condition in which airflow into the lungs decreases markedly (hypopnea) or ceases completely (apnea) for brief periods. These periods of decreased or absent flow (collectively called apneas here) are followed by a ventilatory overshoot during which airflow is high with the result that the increase in carbon dioxide (CO2) and decrease in oxygen (O2) levels in the blood that occurred during the apnea is corrected or overcorrected. Because maintenance of adequate breathing requires certain levels of blood gas tensions, correction or over-correction of blood gas tensions during the overshoot sets the stage for recurrence of the apnea (Younes M. The Physiologic Basis of Central Apnea and Periodic Breathing. Current Pulmonology, 10:265-326, 1989. Younes M. Role of arousals in the pathogenesis of obstructive sleep apnea. Amer J Respir Crit Care Med. 169:623-633, 2004; Younes M. Role of Control Mechanisms in the Pathogenesis of obstructive sleep disorders. J Appl Physiol 105: 1389-1405, 2008). Apneas can be obstructive or central.
The obstructive variety develops when the upper airway (pharynx) is narrow or excessively compliant and collapses under the influence of the negative pressure generated during the inspiratory phase. Normally, the upper airway of such individuals is kept open while awake by activity of pharyngeal muscles called the pharyngeal dilators (Dilators). The activity in these muscles decreases at sleep onset leaving the pharynx with little mechanical support. An apnea develops at sleep onset and continues until the subject awakens or until PCO2 and PO2 levels deteriorate sufficiently to activate the Dilators. When the Dilators are activated by arousal or by blood gas changes, the airway opens. Typically, in patients with obstructive apnea this is associated with a ventilatory overshoot (Overshoot) that overcorrects the blood gas changes, inhibiting the Dilators and resulting in another apnea.
One approach to preventing such recurrences, therefore, is to limit the changes in blood gas tensions that occur during the “open” phase of the cycle. Through such intervention blood gas tensions at the end of the ventilatory phase are not so corrected as to inhibit the Dilators.
The central Apnea variety is also characterized by recurrent cycles of decreased followed by increased flow but the mechanism of this instability is less dependent on upper airway mechanical abnormalities and more related to instability in the mechanisms that regulate blood gas tensions. As in the case of the obstructive variety, the instability may be mitigated by devices that limit the changes in blood gas tensions during the overshoot. Through such intervention blood gas tensions at the end of the overshoot are not so corrected as to inhibit the respiratory centers, thereby mitigating the occurrence of another apnea.
One approach that has been used to mitigate the changes of blood gas tensions during the overshoot is to increase the concentration of CO2 in the inspired gas, through re-breathing or injection of CO2 in the inspired gas. This kind of intervention requires that the patient be connected to the device that alters inspired gas via a facial interface. This is not well tolerated. Furthermore, in my experience the inhalation of CO2 approach is difficult to control and often results in sleep disruption.
A totally new approach to mitigating the changes of blood gas tensions during the overshoot is to mechanically limit the overshoot itself by devices that oppose lung expansion during inspiration. This approach can be implemented by reducing airway pressure at the external airway during inspiration (negative pressure loading) or by application of positive pressure to the external chest wall (thorax and/or abdomen) during inspiration (positive pressure loading).
Negative pressure loading is impractical since it not only requires the poorly tolerated facial interface but the increased negative pressure in the airway will promote more upper airway collapse, which would be counterproductive.
External Positive Pressure Loading, however, can be applied with an inflatable vest or cuff applied to the ribcage and/or abdomen. Such a device would be better tolerated than other approaches that aim to reduce the over-ventilation that occurs at resumption of breathing (e.g. CO2 breathing), or other approaches that are currently used to treat sleep apnea (e.g. Continuous Positive Airway Pressure (CPAP)). In addition, it has the considerable advantage of concomitantly reducing the negativity of intra-thoracic pressure during inspiration, which should mitigate the tendency for the upper airway to collapse during inspiration in susceptible individuals. This latter feature (making intra-thoracic pressure less negative during inspiration) also renders this approach (External Positive Pressure Loading) effective in less severe (than apneas) forms of upper airway dysfunction such as snoring and Respiratory Effort Related Arousals (RERAs).
Snoring: Snoring results from vibration of upper airway wall during breathing. It occurs in subjects with a collapsible airway in whom the abnormality is not severe enough to result in hypopnea or apneas either because the structure of the upper airway is not as abnormal or because the Dilators are more effective in preventing more serious collapse. Snoring is usually most prominent in the inspiratory phase although in some cases respiratory noises can be heard during expiration. In recent years I have been carrying out extensive studies using an approach I labeled Dial-down. In this approach patients with snoring (with or without apneas) are placed on CPAP to normalize their upper airway. On CPAP, upper airway resistance and blood gas tensions are normal and, as a consequence, their respiratory effort (negative intra-thoracic pressure) is not high. Intermittently, we reduce the CPAP level to induce a hypopnea or apnea. With such interventions (Dial-downs) the respiratory drive and effort remain low for a few breaths until the deteriorating blood gas tensions result in an increase in inspiratory effort and more negative intra-thoracic pressure. In my experience with thousands of such Dial-downs in >100 patients, snoring never occurs in the first few breaths after the Dial-down, and only develops sometime later. One possible explanation is that snoring requires high energy to vibrate the soft tissues of the airway and this level of energy develops only when respiratory efforts increase in response to deteriorating blood gas tensions. In such case by use of positive pressure loading during inspiration (as per our proposed invention), intra-thoracic pressure is rendered less negative, which should result in less snoring. It may be argued that the less negative intrathoracic pressure during inspiration will result in less flow and under-ventilation. However, in virtually all cases, snoring is associated with flow limitation at the upper airway. The hallmark of this flow limitation is that flow is independent of downstream pressure (intra-thoracic pressure in this case) or actually decreases as effort increases (Negative Effort Dependence). Thus, by reducing intra-thoracic pressure during inspiration inspiratory flow is not expected to decrease and may actually increase in the presence of Negative Effort Dependence, an added bonus.
Respiratory Effort Related Arousals (RERAs): This is an intermediate phenomenon between snoring and frank obstructive apnea. Here, flow limitation occurs at the upper airway but the level of flow is not sufficient to maintain a steady state. As a result, blood gas tensions slowly but progressively deteriorate resulting in a progressively increasing inspiratory effort and ultimately arousal (arousal occurs when a threshold level of effort (intra-thoracic pressure) is reached). Often flow rate decreases as effort increases in the course of the event. If the progressive decrease in flow rate during the event is related to negative effort dependence, application of external positive pressure during inspiration, by use of the current invention, should mitigate the effort-related decrease in flow. This could delay the arousal, making it possible in some patients to reach a steady state.
Progressive reduction in flow rate: As indicated above, flow rate often decreases breath-by-breath in the course of hypopneas, snoring or RERAs (Younes M. Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea. Amer J Respir Crit Care Med. 168:645-658, 2003; Schwartz A R et al. The hypotonic upper airway in obstructive sleep apnea: role of structures and neuromuscular activity. Am J Respir Crit Care Med 157: 1051-1056, 1998). Also as indicated above, this progressive reduction in inspiratory flow may be related to the progressive increase in inspiratory effort (Negative Effort Dependence). However, certain observations make it likely that other factors contribute to this progressive reduction in inspiratory flow rate. The most important of these observations is that the largest breath-by-breath reduction in inspiratory flow occurs between the first and second breaths of the hypopnea, where the difference in effort is negligible (Younes M. Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea. Amer J Respir Crit Care Med. 168:645-658, 2003). This temporal pattern indicates that the breath-by-breath reduction is, at least in part, related to progressive narrowing of airway dimensions even during expiration (i.e. is independent of instantaneous inspiratory effort). There are several mechanisms that could account for this progressive narrowing during expiration: First, as suggested by Schwartz et al (Am J Respir Crit Care Med 157: 1051-1056, 1998), progressive narrowing is related to progressive reduction in lung volume in the course of the event. Second, as suggested by John Remmers (personal communication), it may be the result of pharyngeal tissues being sucked in during successive inspiratory efforts while failing to completely recoil back during the expiratory phase. Third, as suggested by us (Younes M. Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea. Amer J Respir Crit Care Med. 168:645-658, 2003), progressive narrowing may be related to stress recovery following the phase of open airway. Thus, when the upper airway is widened during the ventilatory phase (or on CPAP) stress relaxation occurs, causing airway dimensions to progressively increase as a function of time. When the dilating force is removed at the onset of hypopnea, stress recovery occurs causing airway dimensions to decrease progressively as a function of time. The second and third mechanisms are both manifestations of visco-elastic behavior of the upper airway (hysteresis in the pressure-area relation) with the only difference between the two being that Remmers' explanation requires successive inspiratory efforts for narrowing to occur whereas with our explanation progressive narrowing would occur even without preceding inspiratory efforts. It is possible/likely that both the second and third mechanisms contribute. We strongly favor visco-elastic behavior (second and/or third mechanisms) over reduction of lung volume (first mechanism) as the cause of progressive narrowing of the airway in the course of obstructive hypopneas and RERAs (Younes M. Contributions of upper airway mechanics and control mechanisms to severity of obstructive apnea. Amer J Respir Crit Care Med. 168:645-658, 2003). Such progressive narrowing in the expiratory phase due to visco-elastic behavior can be reversed by applying positive pressure pulses to the chest/abdomen during expiration using the device of the present invention. These expiratory pulses would force the airway open during expiration, thereby making it easier for the dilators to keep the airway open during inspiration.
It is evident from the above discussion that positive pressure applied externally during the inspiratory phase may be beneficial with certain Sleep Respiratory abnormalities, whereas positive pressure applied externally during the exhalation phase may be beneficial with other abnormalities. It is also clear that these different types of abnormalities may coexist in the same patient. Thus, application of the positive pressure in both phases may also be beneficial. This can take the form of two independent pulses, one during inspiration and one during expiration. Alternatively, the positive pressure may be applied throughout the respiratory cycle. The latter continuous type of pressure application has the potential disadvantage of causing a reduction in lung volume, which is believed to result in narrowing of the upper airway because of reduction in axial traction on the upper airway (as a result of a higher diaphragm position). This complication can be mitigated by applying the continuous pressure only during obstructive events where it cannot reduce lung volume, or by compressing the rib cage only. While compression of the rib cage alone is less effective in increasing intra-thoracic pressure than compression of the rib cage and abdomen together, it has the advantage of forcing the diaphragm downwards, thereby increasing axial traction on the upper airway.